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New Insights on the Mechanisms Affecting Fertility in Men with Non-Seminoma Testicular Cancer before Cancer Therapy

The World Journal of Men′s Health 2020년 38권 2호 p.198 ~ 207
Dias Tania R., Agarwal Ashok, Pushparaj Peter N., Ahmad Gulfam, Sharma Rakesh,
소속 상세정보
 ( Dias Tania R. ) - Cleveland Clinic American Center for Reproductive Medicine
 ( Agarwal Ashok ) - Cleveland Clinic American Center for Reproductive Medicine
 ( Pushparaj Peter N. ) - Faculty of Applied Medical Sciences Center of Excellence in Genomic Medicine Research
 ( Ahmad Gulfam ) - Sydney University School of Medical Sciences Division of Pathology
 ( Sharma Rakesh ) - Cleveland Clinic American Center for Reproductive Medicine

Abstract


Purpose: Patients with non-seminoma testicular cancer (NSTC) cancer can be subfertile or infertile, and present reduced sperm quality, but the underlying mechanisms are unknown. The aim of this study was to compare the sperm proteome of patients with NSTC, who cryopreserved their sperm before starting cancer treatment, with that from healthy fertile men.

Materials and Methods: Semen volume, sperm motility and sperm concentration were evaluated before the cryopreservation of samples from patients with NSTC (n=15) and the control group (n=15). Sperm proteomic analysis was performed by liquid chromatography-tandem mass spectrometry and the differentially expressed proteins (DEPs) between the two groups were identified using bioinformatic tools.

Results: A total of 189 DEPs was identified in the dataset, from which five DEPs related to sperm function and fertilization were selected for validation by Western blot. We were able to validate the underexpression of the mitochondrial complex subunits NADH:Ubiquinone Oxidoreductase Core Subunit S1 (NDUFS1) and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2), as well as the underexpression of the testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (ATP1A4) in the NSTC group.

Conclusions: Our results indicate that sperm mitochondrial dysfunction may explain the observed decrease in sperm concentration, total sperm count and total motile count in NSTC patients. The identified DEPs may serve as potential biomarkers for the pathophysiology of subfertility/infertility in patients with NSTC. Our study also associates the reduced fertilizing ability of NSTC patients with the dysregulation of important sperm molecular mechanisms.

키워드

Cancer therapy; Male fertility; Non-seminoma; Sperm quality; Testicular cancer

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